title: A multicentre randomised trial comparing weekly paclitaxel + S-1 with weekly paclitaxel + 5-fluorouracil for patients with advanced gastric cancer.
abstract: OBJECTIVE
  This study aimed to compare the efficacy and toxicity of weekly paclitaxel plus S-1 with weekly paclitaxel plus 5-fluorouracil in treating advanced gastric cancer as first line regimen. The primary end-point was disease control rate (DCR).
  
  
  METHODS
  Patients with advanced or recurrent gastric cancer were randomly assigned to an experimental arm or a control arm. The experimental arm's dosage schedule was paclitaxel 60 mg/m2 (intravenous infusion) on days 1, 8 and 15 and S-1 80-120 mg/d (oral administration) on days 1-14. Control arm patients were given the same paclitaxel, combined with 5-fluorouracil 500 mg/m2 (continuous intravenous infusion) on days 1-5; and leucovorin 20 mg/m2 (intravenous infusion) on days 1-5. All schedules were repeated every 28 d.
  
  
  RESULTS
  A total of 240 patients were enrolled and equally randomised into two arms. The overall response rate and DCR of the experimental arm was non-inferior to that of the control arm both in the per-protocol set and the full analysis set. The secondary end-point median progression-free survival (PFS) of the experimental and control arms was 153 and 129 d, with the hazard ratio of 0.641 (95% CI: 0.473-0.868, P = 0.004). The hazard ratio of the time to treatment failure of the two arms was 1.449 (95% CI: 0.705-2.980, P = 0.229). The six-month PFS rates of both arms were similar (31.3% versus 31.8%, P = 0.94). Cox regression analysis indicated that only treatment regimen and age were independent predictive factors for PFS. The most common adverse events were haematological and gastrointestinal. The rates of grade 3-4 adverse events were not significantly different between the two study arms and were mostly lower than 5%.
  
  
  CONCLUSIONS
  Weekly paclitaxel combined with S-1 is an active and well-tolerated regimen, supporting the view that S-1 can be an alternative for infusional 5-fluorouracil for advanced gastric cancer.
authors.affiliation: Department of Gastrointestinal Medical Oncology, Tianjin Medical University Cancer Institute & Hospital, Tianjin, China.
authors.forename: Dingzhi
authors.initials: D
authors.lastname: Huang
authors.forename: Yi
authors.initials: Y
authors.lastname: Ba
authors.forename: Jianping
authors.initials: J
authors.lastname: Xiong
authors.forename: Nong
authors.initials: N
authors.lastname: Xu
authors.forename: Zhao
authors.initials: Z
authors.lastname: Yan
authors.forename: Zhixiang
authors.initials: Z
authors.lastname: Zhuang
authors.forename: Zhuang
authors.initials: Z
authors.lastname: Yu
authors.forename: Huiping
authors.initials: H
authors.lastname: Wan
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhang
authors.forename: Ting
authors.initials: T
authors.lastname: Deng
authors.forename: Rongsheng
authors.initials: R
authors.lastname: Zheng
authors.forename: Zengqing
authors.initials: Z
authors.lastname: Guo
authors.forename: Chunhong
authors.initials: C
authors.lastname: Hu
authors.forename: Meiling
authors.initials: M
authors.lastname: Wang
authors.forename: Zhonghe
authors.initials: Z
authors.lastname: Yu
authors.forename: Yang
authors.initials: Y
authors.lastname: Yao
authors.forename: Jichang
authors.initials: J
authors.lastname: Meng
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D000855:Anorexia / Q000139:chemically induced; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D004338:Drug Combinations; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D007262:Infusions, Intravenous; D053208:Kaplan-Meier Estimate; D002955:Leucovorin / Q000008:administration & dosage / Q000009:adverse effects; D007970:Leukopenia / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009325:Nausea / Q000139:chemically induced; D010094:Oxonic Acid / Q000008:administration & dosage / Q000009:adverse effects; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology; D005641:Tegafur / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D004338:Drug Combinations; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D017239:Paclitaxel; D002955:Leucovorin; D005472:Fluorouracil
keywords: Efficacy; Gastric cancer; Paclitaxel; S-1; Safety